Studies are proposed to determine the sites and mechanisms of action of amphetamine, a widely abused psychomotor stimulant drug. Changes in neuronal activity in the substantia nigra and neostriatum will be recorded in rats in response to amphetamine administered intravenously or by means of local microinfusion into the substantia nigra or neostriatum. Of special interest will be whether the effects of amphetamine on neuronal activity in these regions are altered by long-term amphetamine pretreatment for periods of from one to two weeks and in doses of 5 or 10 mg/kg daily. Statistical analysis of spontaneously active neurons in the neostriatum (autocorrelation and cross-correlation analysis) will be undertaken in an effort to reveal characteristic firing patterns of neostriatal elements and their potential synaptic interactions. A quantitative analysis of the ultrastructural appearance of the substania nigra and neostriatum will be carried out in saline treated as well as amphetamine pretreated animals utilizing the electron microscope. The possibility of the existence of presynaptic dendrites in the substantia nigra and locus coeruleus will be assessed by studying serial sections through these regions in animals treated with intraventricular 5-hydroxydopamine in which monoaminergic dendritic and axonal profiles may be distinguished. The quantitative distribution and appearance of varying categories of synaptic profiles, both labelled and non-labelled in substantia nigra and neostriatum will be compared in animals given saline or long-term amphetamine treatment to determine if toxic morphological effects can be detected.